Previous work has demonstrated that beta-guanidinopropionic acid (beta GPA) competes with creatine for transport into rat skeletal muscle and that feeding beta GPA to rats results in depletion of creatine and N-phosphorylcreatine (CP) from skeletal muscle. The objective of the present work is to evaluate the need for creatine and CP in skeletal muscle metabolism by evaluating the consequences of specifically depleting muscle of these compounds. First, the best animal model for such studies will be selected, and it will be determined that beta GPA has no toxicity for the animal other than that which may be due to creatine and CP depletion. Then the processes of anaerobic glycolysis and oxidative metabolism of skeletal muscle of beta GPA-fed animals will be studied to identify compensatory changes induced by creatine and CP depletion. In addition the metabolism of beta GPA will be studied with the aid of C14-labelled beta GPA. These studies should provide basic information about the metabolic adaptations of muscle and especially about their interrelationships. This information should make it possible to decide whether or not a primary lesion of creatine metabolism would be sufficient to cause significant muscle disease.